OBJECTIVE: To evaluate the effectiveness of the omeprazole, amoxicillin, and clarithromycin (OAC) regimen in eradicating H. pylori (HP) in patients on long term acid suppression medicine for documented ulcer or ulcer like symptoms. METHODS: Kaiser Permanente data bases were accessed to identify all patients receiving acid suppression therapy for at least three 30-day periods within the most recent 12-month time frame. Those identified were then matched to databases that capture physician recorded diagnoses at each patient visit. Patients not previously treated for HP and with documented (by endoscopy or UGI) diagnoses of duodenal ulcer (DU), gastric ulcer (GU), gastritis, and unspecified peptic ulcer disease (PUD) or ulcer like symptoms were selected for recruitment. Study participants were randomly assigned to C14 urea breath testing (UBT) and HP eradication, if positive, versus standard maintenance acid suppressive therapy. All patients positive on UBT (except those allergic to penicillin N=12) were treated with omeprazole 20 mg, amoxicillin 1gm, clarithromycin 500 mg bid for 10 days. Proof of eradication was documented by UBT administered 4 weeks post treatment. Each patient testing negative after treatment was taken off acid reducing medication and followed for up to one year. RESULTS: Ninety-five of 96 patients completed 10 days of OAC, and 89 have been retested 4 weeks later. Of those retested, 85% (95% CI=76%, 92%) were breath test negative and 15% (95% CI=8%, 24%) were breath test positive. Fourteen participants reported recurrent symptoms following HP eradication. Side effects of patients on the regimen were reported by 6 out of 96 treated (6%), and included bloody diarrhea (1), rash (4), and abdominal cramps (2). CONCLUSION: OAC is an effective regimen for eradicating HP in infected patients on chronic acid suppression for PUD or ulcer like symptoms. Compliance with the regimen is high and serious adverse reactions are low.